Hedgehog control of resident vascular stem cell niches

Cardiovascular disease (CVD) is a major cause of death for Irish people killing 1 in 3 every year. Most of the problems associated with CVD are due to changes in the structural integrity of the blood vessel wall resulting in obstruction of blood flow that can lead to a heart attack or stroke. Key cells involved in this blockage are called vascular smooth muscle cells (SMC). Despite intensive efforts, the source of these cells remains controversial. Emerging evidence now suggests that specialised cells called stem cells are present within the vessel wall and become vSMC during disease progression to cause the obstruction. In addition, it is known that the origin of the cells during development directly impacts on the likelihood of the vessel becoming obstructed. This proposal will examine how these specialized adult stem cells within the vessel wall are maintained and become SMC over time and whether their ability to respond is dictated in part by their particular origin during early developemnt. To address this question, we will compare the response of these vessel wall stem cells from different regions of the aorta of discrete developmental origin to a specific stimulus, in this case a regulating factor called sonic hedgehog. The outcome of this work will greatly enhance our understanding of how stem cells contribute to vascular disease while presenting unique opportunities to design novel drugs to combat the 'pro-vascular disease' role of these cells.